Elucidating the efficacy and mechanism of Ginkgo biloba extract in treating hyperuricemic nephropathy using network pharmacology, metabolomics, gut microbiota analysis, and experimental validation

Abstract Background Although Ginkgo biloba extract (GBE) has been used to treat nephropathy, its effects and underlying mechanisms in hyperuricemic nephropathy (HN) remain unclear. Methods Based on biochemical parameters, inflammatory markers, and renal histopathological morphology, this study employed a rat HN model to examine the impact of GBE. Subsequently, an integrated strategy—combining network pharmacology, renal metabolomics, and gut microbiota profiling—was implemented to probe the mechanistic basis. Finally, Molecular dynamics (MD), molecular dynamic simulations, polymerase chain reaction (PCR), immunohistochemistry (IHC), and xanthine dehydrogenase (XDH) inhibits were applied to elucidate the mechanisms. Results The similarity of fingerprint profiles of three batches of GBE was >0.95, with flavonoid and lactone contents of 29.94% and 13.78%, respectively, meeting the requirements of the Chinese Pharmacopeia standards. GBE intervention led to improved renal function, lowered concentrations of uric acid (UA), interleukin-1 beta, and interleukin-6, and alleviated renal injury. It also regulated purine metabolism and gut microbiota. Notably, quercetin in GBE strongly inhibited xanthine dehydrogenase, as confirmed by its low binding energy and reduced renal expression. Conclusions GBE alleviates HN through a dual mechanism: by targeting the purine metabolism pathway to inhibit UA production and by modulating the gut microbiota to restore homeostasis. These findings provide insights into the molecular mechanisms underlying the therapeutic effects of traditional Chinese medicine in HN.